Europe, U.S. Cooperate on Drug Regulation

Medication safety can be seen as a global concern requiring close collaboration

Thomas Reinke

Globalization of drug development and drug marketing has spawned a movement, though small, toward international drug regulation. In a Dec. 15, 2010 interview with the Wall Street Journal, Thomas Lonngren, outgoing head of the European Medicines Agency, which approves drugs in Europe, said the FDA and EMA are working together on drug approvals.

A day later came this headline on an FDA news release: “FDA begins process to remove breast cancer indication from Avastin label.”

Simultaneously, a news release from London read, “European Medicines Agency completes its review of Avastin used in breast cancer.”

First there was Avandia

The two agencies took coordinated action to curtail the use of Avastin (bevacizumab). The EMA’s action was definitive; it eliminated authorization for one select combination therapy while allowing continued use in another combination therapy.

The FDA’s announcement signaled its intention to totally remove approval for the breast cancer indication. However, one final step remained open: the option for an appeal by Roche, Avastin’s manufacturer. Roche filed that appeal and the drug remains available. The FDA may grant or deny that hearing.

Avastin is used in combination with other agents to treat colon, rectum, lung, kidney, or breast cancer. The actions of the two agencies do not affect its use for the other indications.

This was the second time the two agencies have worked together. In September 2010 they came out against GlaxoSmithKline’s Avandia, a diabetes drug with heart attack risks. The actions on Avandia were the mirror image of the current situation. It was banned in Europe and only restricted in this country. The result sealed Avandia’s fate, although sales had fallen dramatically before the announcements: Roche now projects minimal sales.

Lonngren said the timing of the Avandia announcements was deliberate, and he was quoted as saying this was an “example of how enforcement will be done in the future.”

The actions so far have focused on drug safety, not new drug approvals. Global distribution of medications means that when safety concerns arise in one country, there are worldwide implications. The need for cooperation is clear. Furthermore, clinical trial data are easily available worldwide, and regulatory agencies certainly should consider all credible information that is available to them.

Cooperation may give leverage to evidence-based drug decisions, because concern may arise when one regulatory agency takes action but another doesn’t. A decision by one agency can be criticized by citing the other agency’s inaction. The credibility and responsiveness of one agency may also come into question.

Cooperation may also benefit the regulators in emotionally charged situations. The FDA’s Avastin decision produced a significant backlash, including a sensationalistic post, “The Death Panel’s First Murder,” on the American Spectator’s blog. It speculated on the possibility of more breast cancer deaths and called the FDA ruling a bureaucratic, elitist, and authoritarian command.

Head vs. heart

Emotional and political decisions can override science, such as the November 2009 recommendation of the U.S. Preventive Services Task Force to change the recommendation for mammograms to age 50 from age 40. It was overridden in the Affordable Care Act with mandatory coverage of mammograms beginning at age 40.

The FDA originally approved Avastin under its accelerated approval program, but later studies showed risks to outweigh benefits.

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